Innovation in pediatric heart transplantation

The Children's Hospital of Wisconsin heart transplant team has contributed numerous clinical and research innovations that have changed the standard of care throughout the heart transplant community. These include:

  • Development of The Virtual Crossmatch
  • Development of a novel blood test to detect rejection
  • Creation of a new MRI-validated technique for size matching
  • Use of rotational angiography to assess coronary arteries
  • Development of a protocol to manage a positive crossmatch

Read more about our innovation in heart transplantation below:

Development of The Virtual Crossmatch

The Virtual Crossmatch is a tool that makes it easier and safer to transplant patients with antibody sensitization.

When a person is exposed to blood or tissue from another person (either through a blood transfusion, during heart surgery, with a homograft or tissue graft, or even during pregnancy) their immune system can make antibodies against cell markers from that other person. This can make it harder to find a match for them later in life if they need an organ transplant. This is called antibody sensitization. In the past, most centers would solve this problem by listing patients who have these types of antibodies with the requirement for a "prospective crossmatch." This means they would only be able to accept a heart from a nearby center where they could test a sample of the donors blood with that of the recipient to see if the match was right. Unfortunately, this led to much longer wait times for sensitized patients and tragically a higher risk of death while waiting.

In 2003, researchers at the Children's Hospital of Wisconsin decided to apply high resolution flow cytometry to the problem. We hypothesized that we can use flow cytometry to identify exactly which antibodies a person has and use this to make decisions about whether a heart donor would be a good match without requiring direct blood to blood testing. We ran a series of test donors against a single recipient; a child who had been waiting on the list at our center for more than 2 years, using blood samples donated to the Blood Center of Wisconsin. The test was highly successful. We called this a "Virtual Crossmatch" [REF] and reported our results in a manuscript published in the journal Pediatric Transplantation.

More impressively, we started applying this to our own patients including the little boy who was our original test case. After 2 years, we reported our outcomes using this approach in another research paper entitled "The Practical Application of the Virtual Crossmatch" [REF].

In our experience, we compared our outcomes with patients listed historically at our center with the sensitized patients using the virtual crossmatch. The prospective crossmatch included 8 patients with 7 out of 8 who died while waiting and using the virtual crossmatch, we had 10 patients, with 9 out of 10 being transplanted by the time of publication with 100% survival. Virtual Crossmatching has now become the standard of care across the world and we continue to make improvements to our process. According to UNOS, In 2005 – 14.3% of pediatric heart transplant listings required a prospective crossmatch, in 2012, that number has dropped to 1.7% despite a higher proportion of sensitized recipients.

Development of a novel blood test to detect rejection

The heart transplant team developed a novel blood test to detect rejection in heart transplant patients as an alternative to surveillance heart biopsies. Read more >>

Creation of a new MRI-validated technique for size matching

The heart transplant team created a new Magnetic Resonance Imaging (MRI) validated technique using echocardiography to size match donors and recipients.

Size matching in pediatric heart transplantation between donors and recipients can be a real challenge. The heart size of children listed for transplant can be highly variable; some children with cardiomyopathy may have a very large dilated heart while some patients with congenital heart disease may have an abnormally small heart with less than the normal four heart chambers.

Currently, centers use weight of the donor and recipients to make these decisions along with the eyeball test of the size of the heart on Chest X Rays. This is an important issue because accepting an undersized heart increases the risk of early graft failure and an oversized graft can cause problems with the lungs and preclude closure of the chest immediately after the surgery.

We developed an approach that gets right to the heart of the problem. We wanted to eliminate surrogate measures and actually come up with a more direct way to compare the size of the heart of our patient on the waiting list with the actual size of the heart of the donor. We used MRI to measure the total cardiac volume of a series of patients and then developed a relatively simple technique using echocardiography to directly obtain a measured estimate of heart size.

We validated the echo measurement with the MRI measurement and showed that the measurements correlated very well. We also found that we could use a single standard echo measurement for donors, taking advantage of the fact that donor hearts are by definition "normal" in size. This allows us to have a measurement of heart size for our listed patient and back calculate a target volume measurement for a normal donor so that at the time of an offer, we can immediately compare measures of the size of the donor and the recipient heart [REF].

Use of rotational angiography to assess coronary arteries

The heart transplant team used a process called rotational angiography to improve coronary artery screening for heart transplant recipients.

Patients who receive heart transplants are at risk for developing problems with their coronary arteries (graft vasculopathy). For this reason, cardiologists use cardiac catheterization to allow direct access to the coronary arteries to inject contrast to take pictures. We took advantage of new technology in the cardiac catheterization laboratory to use a process called rotational angiography to get more information out of each injection. This method uses a camera that swings around the patient in real time essentially taking a movie during a single injection allowing visualization of the coronary artery from a wide arc of different angles. This may improve accuracy, shorten procedure time and may allow in some cases for less contrast and radiation exposure [REF].

Development of a protocol to manage a positive crossmatch

The heart transplant team developed a peri-operative protocol to improve outcomes for heart transplant patients with a positive crossmatch.

While we have pioneered the use of the virtual crossmatch for patients with pre-formed antibodies, we recognize that not all patients can wait for a negative crossmatch because they just have too many antibodies. We have therefore developed a protocol which allows us to perform a transplant despite a positive crossmatch in such a way as to minimize the added risk. In these cases, we still use our virtual crossmatch to select an organ with the lowest number of donor specific antibodies – in other words, not a perfect match, but a better than random match. Read the abstract >>